Detection and Characterization of Blood-borne Prions

血源性朊病毒的检测和表征

• 批准号: 10625408
• 负责人: Candace K. Mathiason
• 金额: $ 46.42万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625408
• 关键词: Affect; Agriculture; American; Amyloid; Animals; Asia; Biological; Biological Assay; Blood; Blood Cells; Blood Platelets; Blood Transfusion; Blood specimen; Canada; Cell Fraction; Centrifugation; Chronic Wasting Disease; Chronology; Clinical; Collaborations; Collection; Consumption; Coupled; Creutzfeldt-Jakob Syndrome; DNA Sequence Alteration; Deer; Detection; Disease; Drosophila genus; Economics; Environment; Europe; Excretory function; Genetic; Genetic Carriers; Grant; Health; Hematogenous; Human; Industry; Infection; Kinetics; Label; Letters; Leukocytes; Methodology; Methods; Monitor; Nature; Oral; Pathogenesis; Patients; Phenotype; Population; PrP; Prevalence; Prion Diseases; Prions; Reindeer; Research; Risk; Safety; Sampling; Scrapie; Sheep; Sorting; Testing; Therapeutic; Time; Tissues; Transgenic Mice; Translating; Variant; Zoonoses; cervid; cost effective; improved; in vitro Assay; in vivo; inhibitor; magnetic beads; mutation carrier; pre-clinical; prevent; prion seeds; prototype; trafficking; translational impact; transmission process

No practical noninvasive antemortem test exists to detect cervid, human, or any, prion disease. Blood- borne transmission of prions from asymptomatic human variant Creutzfeldt Jakob Disease (vCJD)-infected humans has occurred(12,14-16). Chronic wasting disease (CWD) is an emergent rapidly spreading disease in cervids(27,28,37-40) with uncertain zoonotic potential(3-8). An estimated one in 36 Americans hunt deer and/or elk, resulting in an estimated 7,000-15,000 CWD-infected cervids consumed annually in the USA (increasing 20%/yr)(2). As hunting is a roughly $26 billion (per annum) industry(1), CWD represents an enormous potential health and economic threat. The commonalities among vCJD and cervid CWD, including the presence of hematogenous infectivity(34,47), are remarkable. Antemortem detection and surveillance of human, and animal, prion disease has been hindered by the combination of low prion concentrations and abundant assay inhibitors in blood and other accessible biological samples. We have developed simple, rapid, specific and highly sensitive in vitro assays to detect blood-borne prions(9-11). In this competing renewal we will quantitate the temporal distribution and specific blood cell phenotypes critical to prionemia in serially-collected human and cervid blood samples. The translational impact of the results of these studies will: a) improve human blood transfusion safety, b) provide a better means to assess and monitor developing prion therapeutics, c) largely eliminate the risks of human consumption of cervid prions, d) provide greater understanding of the prevalence and consequences of CWD to the cervid hunting and agriculture industries, and e) elucidate our understanding of prionemia in disease pathogenesis. Thereby, this research will have immediate impacts in both human and animal health.

没有实用的非侵入性生前测试存在检测鹿，人类，或任何，朊病毒疾病。血- 无症状人类变异型克雅氏病（vCJD）感染者的朊病毒传播 人的存在（12，14 -16）慢性消耗性疾病（CWD）是一种突发性、快速传播的疾病， 鹿科动物（27、28、37 -40），具有不确定的人畜共患病潜力（3-8）。据估计，每36个美国人中就有一个猎鹿和/或 麋鹿，导致估计每年在美国消费7，000 - 15，000只感染CWD的鹿科动物（增加 20%/年）（2）。由于狩猎是一个大约260亿美元（每年）的行业（1），CWD代表了巨大的潜力 健康和经济威胁。vCJD和cervid CWD之间的共同点，包括存在 血行感染性（34，47）是显著的。人的死前检测和监测，以及 在动物中，朊病毒疾病受到朊病毒低浓度和丰富的 测定血液和其他可获得的生物样品中的抑制剂。我们开发了简单，快速， 特异性和高灵敏度的体外试验，以检测血液传播的朊病毒（9-11）。在这场竞争性的更新中，我们将 在连续收集的样本中定量时间分布和对朊病毒血症至关重要的特定血细胞表型， 人类和鹿的血液样本。 这些研究结果的翻译影响将： a）提高人体输血安全性， B）提供更好的方法来评估和监测朊病毒治疗剂的开发， c）在很大程度上消除人类食用鹿朊病毒的风险， d）使人们更好地了解慢性消耗病对鹿狩猎的普遍性和后果， 农业产业，以及 e）阐明我们对朊病毒血症在疾病发病机制中的理解。 因此，这项研究将对人类和动物健康产生直接影响。

项目成果

Genetic modulation of CWD prion propagation in cervid PrP Drosophila.

• DOI: 10.1042/bcj20230247
• 发表时间: 2023-10-11
• 期刊: The Biochemical journal

PrPSc formation and clearance as determinants of prion tropism.

PrPSc 的形成和清除是朊病毒趋向性的决定因素。

• DOI: 10.1371/journal.ppat.1006298
• 发表时间: 2017
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Shikiya,RonaldA;Langenfeld,KatieA;Eckland,ThomasE;Trinh,Jonathan;Holec,SaraAM;Mathiason,CandaceK;Kincaid,AnthonyE;Bartz,JasonC
• 通讯作者: Bartz,JasonC

Aspects of the husbandry and management of captive cervids.

• DOI: 10.1038/laban.972
• 发表时间: 2016-04
• 期刊: Lab animal
• 影响因子: 6.9
• 作者: McNulty E;Selariu AI;Anderson K;Hayes-Klug J;Nalls AV;Powers JG;Hoover EA;Mathiason CK
• 通讯作者: Mathiason CK

Silent Prions and Covert Prion Transmission.

沉默朊病毒和隐蔽朊病毒传播。

• DOI: 10.1371/journal.ppat.1005249
• 发表时间: 2015
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Mathiason,CandaceK

Expression of the cellular prion protein by mast cells in the human carotid body.

• DOI: 10.1080/19336896.2023.2193128
• 发表时间: 2023-12
• 期刊: PRION
• 影响因子: 2.3
• 作者: Sweetland, Gregory D. D.;Eggleston, Connor;Bartz, Jason C. C.;Mathiason, Candace K. K.;Kincaid, Anthony E. E.
• 通讯作者: Kincaid, Anthony E. E.